New method shows how bacteria become dangerous pathogens

Two new papers published this month reveal how bacteria can become dangerous pathogens
through completely different routes. One paper shows how a bacterium responsible for serious
infection in newborns gained an advantage because it acquired resistance to an antibiotic, and
the other paper shows it is likely that changes in the environment helped a typhoid-causing
bacterium to gain a foothold in human populations.

The papers describe a new approach that combines whole genome sequencing - an ability to
analyze the genetic code of bacteria in great detail - with phylogenetic reconstruction - an
ability to trace the family tree of different strains of the same organism back to a common
ancestor.

Gordon Dougan, a professor from the Wellcome Trust Sanger Institute in Hinxton, near Cambridge
in the UK, and co-author of both papers, explains:

"We have developed systems for characterising the population structure of pathogens, and used
these systems in two instances to yield different findings. We were able to define the timeframe
of the origin of two completely different infectious diseases, and in future we will be able to
use this approach to identify and control emerging threats."

Typhoid fever likely emerged from changes in human living conditions

In the Proceedings of the National Academy of Sciences, Prof. Dougan and colleagues
describe how they worked out that Salmonella enterica serovar Paratyphi A, which causes
typhoid fever, emerged in humans about 450 years ago, but since then it has remained genetically
similar.

The team suggests Paratyphi A moved from animals to humans when we started living in close proximity to livestock.

Over the centuries, Paratyphi A appears to have accumulated genetic mutations - not as a
result of any particular event, but through a gradual process known as genetic drift.

The researchers suggest the disease may have moved from animals to humans when people began to
inhabit denser environments and started living close to their livestock. They suggest the
bacterium followed a similar path to whooping cough and tuberculosis - it became fixed in humans
and spread around the world.

The team also found evidence that in recent decades, the bacterium has begun to change due to
use of antibiotics, although those mutations are not currently very stable.

The researchers hope their findings will help scientists understand how the pathogen manages
to travel within and across human populations, and how its genes change over time. The findings
are also timely in that vaccines for Paratyphi A are currently in development and trials should
start within the next 3 years.

Tetracycline may have helped GBS become a threat to newborn babies

In the other paper, published in Nature Communications, Prof. Dougan and another set
of colleagues traced the genetic development of the bacterium Streptococcus agalactiae
or Group B Streptococcus (GBS), a cause of serious septicemia and shock in newborns.

In this case, they found evidence that the disease emerged in the 1960s, not primarily
because of previous under-diagnosis, as widely believed, but more likely because the pathogen
acquired genes that made it resistant to the broad-spectrum antibiotic tetracycline.

Over-use of tetracycline led to an evolutionary bottleneck, allowing GBS strains to acquire
genes that make it resistant to the drug, transforming a harmless organism into a pathogen that
found a niche in mothers and their newborns.

Tetracycline may also give GBS another advantage by eliminating the thousands of friendly
species of microorganisms living in the microbiomes of mothers and babies, which may stop GBS
becoming too dominant.

The paper offers insight into another route through which an infectious disease can emerge -
this time through inadvertent use of drugs, as Prof. Dougan explains:

"This is possibly the earliest case of the emergence of a new disease that can be directly
associated with antibiotic use. GBS causes a distressing infection of sepsis and meningitis seen
in newborn children that can result in severe illness and death, making it one of the most
serious diseases in babies."

Meanwhile in June 2014, Medical News Today learned of a breakthrough in the fight
against drug-resistant bacteria. A team at the University of East Anglia in the UK has discovered
how the defensive barriers of superbugs are built, a finding that could help develop new drugs to which bacteria cannot develop
resistance.

Please note: If no author information is provided, the source is cited instead.

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